Retrospective Study Open Access
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Apr 27, 2025; 17(4): 102697
Published online Apr 27, 2025. doi: 10.4240/wjgs.v17.i4.102697
Risk factors for bile leakage after laparoscopic common bile duct exploration in older patients with choledocholithiasis
Ruo-Fei Xiong, Zhi-Ming Wu, Hong-Jun Huang, Department of General Surgery, Shaoxing Central Hospital, Shaoxing 312000, Zhejiang Province, China
Shan-Shan Lu, Department of Geriatrics, Shaoxing University Affiliated Hospital, Shaoxing 312000, Zhejiang Province, China
Tao Xiao, Department of General Surgery, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
ORCID number: Ruo-Fei Xiong (0009-0002-0434-716X); Tao Xiao (0000-0002-7849-4675).
Co-first authors: Ruo-Fei Xiong and Shan-Shan Lu.
Author contributions: Xiong RF, Lu SS, and Wu ZM were responsible for the conception and design of the study and drafting the article; Xiong RF and Lu SS contributed equally to this article as co-first authors; Xiong RF, Lu SS, Wu ZM, and Huang HJ contributed to the data analysis and interpretation; Huang HJ contributed to acquisition of the data; Xiao T was responsible for revising the manuscript critically for important intellectual content, and final approval of the version to be submitted; and all authors thoroughly reviewed and endorsed the final manuscript.
Supported by the Ke Qiao Science and Technology Plan Projects, No. 2022KZ70.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Shaoxing Central Hospital, approval No. 2023029.
Informed consent statement: The need for patient consent was waived due to the retrospective nature of the study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Dataset is available from the corresponding author by e-mail at xiaotao@ncu.edu.cn.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Tao Xiao, MD, Department of General Surgery, First Affiliated Hospital of Nanchang University, No. 17 Yong Wai Zheng Street, Nanchang 330006, Jiangxi Province, China. xiaotao@ncu.edu.cn
Received: October 28, 2024
Revised: January 13, 2025
Accepted: February 12, 2025
Published online: April 27, 2025
Processing time: 154 Days and 16.3 Hours

Abstract
BACKGROUND

At present, there are few studies on the risk factors for bile leakage after laparoscopic common bile duct exploration (LCBDE) for older patients with choledocholithiasis.

AIM

To identify the potential risk factors for bile leakage after LCBDE in older patients.

METHODS

A retrospective, single-center observational analysis was performed on patients aged ≥ 70 years with choledocholithiasis treated by LCBDE who were admitted to our center between January 2011 and August 2022. The included patients were divided into non-bile leakage and bile leakage groups. Risk factors were determined by analyzing the observation indicators.

RESULTS

Seventy older patients with choledocholithiasis who underwent LCBDE were included. Univariate analysis showed that positive culture of bile bacteria was a risk factor for bile leakage after LCBDE (P < 0.05). We further analyzed the bile bacteria, and univariate analysis showed that Enterococcus faecalis (E. faecalis) (P < 0.05) and Pseudomonas aeruginosa (P < 0.05) were associated with an increased risk of postoperative bile leakage in older patients (P < 0.05). Multivariate analysis showed that E. faecalis was an independent risk factor for postoperative bile leakage in older patients (P < 0.05). The results of antibiotic sensitivity analysis showed that E. faecalis had 100% susceptibility to penicillin, ampicillin, linezolid, vancomycin, and furantoin.

CONCLUSION

E. faecalis-associated biliary tract infection is an independent risk factor for bile leakage after LCBDE in older patients with choledocholithiasis. We suggest coverage with antibiotics to which E. faecalis is sensitive.

Key Words: Bile leakage; Common bile duct stones; Older patients; Laparoscopic common bile duct exploration; Enterococcus faecalis; Antibiotic sensitivity

Core Tip: This is a retrospective single-center observational study to investigate the potential risk factors for bile leakage after laparoscopic common bile duct exploration in elderly patients. Enterococcus faecalis (E. faecalis) is an independent risk factor for postoperative bile leakage in elderly patients. The results of drug sensitivity analysis showed that E. faecalis was fully sensitive to penicillin, ampicillin, linezolid, vancomycin, and furantoin. In elderly patients with choledocholithiasis who are at risk of postoperative bile leakage, we suggest covering sensitive drugs for E. faecalis in the empiric regimen of antibiotics.



INTRODUCTION

According to the “2022 Revision of World Population Prospects”, published by the United Nations (https://population.un.org/wpp/), the world’s population is aging. One of the effects of an aging population is the increase in health problems of older people. The proportion of older patients requiring surgery is gradually increasing. However, increasing age itself is an important risk factor for postoperative morbidity and mortality[1]. Therefore, older patients are often considered to be at greater risk of surgical complications than younger patients.

Choledocholithiasis (common bile duct stones, CBDSs) is a common disease in clinical settings and occurs in 10%-20% of patients with gallstones, and the incidence of bile duct stones increases with age[2]. Patients with CBDSs often experience abdominal pain, fever, acute cholangitis, acute pancreatitis, obstructive jaundice, secondary biliary cirrhosis, and other symptoms. In serious cases, CBDSs may be fatal[3]. At present, there are two conventional methods for the treatment of CBDSs: Endoscopic retrograde cholangiopancreatography (ERCP)/endoscopic stone extraction and common bile duct exploration. Although ERCP treatment for CBDSs is widely favored[4], in some cases with large or multiple stones, ERCP often fails to remove the stones successfully[5-7], especially in older patients, in whom the failure rate is reported to be as high as 20%[8,9]. At this time, common bile duct exploration becomes the only effective method[10]. Laparoscopic common bile duct exploration (LCBDE) has the advantages of less trauma, faster recovery, and a similar postoperative complication rate compared with traditional open common bile duct exploration[11], and it has gradually replaced the open procedure. Bile leakage is a serious complication after LCBDE; in severe cases, bile leakage causes abdominal sepsis and may result in death[12]. The immune system and resistance of older patients are weaker, and they often have comorbid heart disease, cerebrovascular disease, pulmonary disease, diabetes mellitus, and other related diseases. Therefore, when bile leakage occurs in patients with CBDSs after surgery, the risk of death is increased[13-16]. Therefore, it is important to identify the potential risk factors for bile leakage after LCBDE in older patients and reduce the incidence of postoperative bile leakage.

MATERIALS AND METHODS
Patients

This was a retrospective analysis of older patients (≥ 70 years old) with CBDSs who were admitted to our center between January 2011 and August 2022. According to the treatment plan, the patients were divided into non-bile leakage and bile leakage groups after LCBDE. The study was approved by the Ethics Committee of our center (approval No. 2023029). Patient consent to review medical records was granted by the Institutional Ethics Committee. The handling of the patient data confidentiality strictly followed the rules set by the institution and complied with the Declaration of Helsinki.

Inclusion and exclusion criteria

Inclusion criteria: (1) Age ≥ 70 years; and (2) Patients were selected for LCBDE after they had a diagnosis of CBDSs confirmed by preoperative abdominal ultrasonography and/or magnetic resonance cholangiopancreatography (MRCP). All cases were confirmed to have no stone residue by imaging review (MRCP examination, T-tube cholangiography, indwelling nasobiliary cholangiography, etc.) after LCBDE.

Exclusion criteria: (1) Patients who were confirmed by preoperative MRCP or preoperative abdominal ultrasonography to have hepatolithiasis or congenital choledochal cysts; (2) Patients with complicated malignant tumors, such as those of the liver, gallbladder, bile duct, duodenal papilla, or pancreas; (3) Patients with common bile duct stenosis or intraoperative exploration of the lower end of the common bile duct obstruction; (4) Patients with structural variants of the bile duct; and (5) Patients with choledochojejunostomy or a history of choledochojejunostomy. We referred to studies on bile leakage published by the American Medical Association (2006) and the Society for Surgery of the Alimentary Tract (2008). The definition of bile leakage was as follows: Bile or fluid containing bile was detected in the drainage tube for > 3 days, and the volume of drainage containing bile was > 50 mL/day[17,18].

Selection of observation indicators

Observational indicators that were available were selected for statistical analysis, including sex, age, diabetes mellitus, hypertension, preoperative pulmonary disease, heart disease, cerebrovascular disease, American Society of Anesthesiologists score, viral hepatitis B, preoperative white blood cell count (< 10 × 109/L vs ≥ 10 × 109/L), percentage of neutrophils (< 70% vs ≥ 70%), hemoglobin (< 120 g/L vs ≥ 120 g/L), total bilirubin (< 34.2 mmol/L vs ≥ 34.2 mmol/L), direct bilirubin (< 17.1 mmol/L vs ≥ 17.1 mmol/L), indirect bilirubin (< 17.1 mmol/L vs ≥ 17.1 mmol/L), alanine transaminase (< 80 U/L vs ≥ 80 U/L), aspartate aminotransferase (< 70 U/L vs ≥ 70 U/L), alkaline phosphatase (< 100 U/L vs ≥ 100 U/L), γ-glutamyl transpeptidase (< 45 U/L vs ≥ 45 U/L), total bile acid (< 13 mmol/L vs ≥ 13 mmol/L), total cholesterol (< 5.7 mmol/L vs ≥ 5.7 mmol/L), high-density lipoprotein cholesterol (< 1.55 mmol/L vs ≥ 1.55 mmol/L), low-density lipoprotein cholesterol (< 3.36 mmol/L vs ≥ 3.36 mmol/L), amylase (< 133 U/L vs ≥ 133 U/L), total protein (< 65 g/L vs ≥ 65 g/L), albumin (< 35 g/L vs ≥ 35 g/L); associated cholecystectomy (yes vs no), stone position (bounded by the gallbladder duct: Upper and lower ends), number of stones (≤ 1 vs > 1), stone size (< 10 mm vs ≥ 10 mm), diameter of the common bile duct (< 10 mm vs ≥ 10 mm), operation mode (primary duct closure), T-tube drainage, primary duct closure + endoscopic nasobiliary drainage, abdominal surgery history (yes vs no), periampullary diverticula (yes vs no), postoperative fasting time (≤ 1 day vs > 1 day), and bacterial culture of bile (negative vs positive).

Bile bacterial cultures were derived from bile extracted after incision of the common bile duct. Samples were transferred to the microbiology department within 2 hours of collection and cultured according to the laboratory standard procedure. Bacterial identification and drug susceptibility tests were performed using the French Bio-Merieux ATB-Expression Automatic Bacterial Identification and Drug Susceptibility Test instrument. The results were evaluated based on the 2010 recommendations of the American Society for Clinical Laboratory Standardization Antimicrobial Susceptibility Test Standards.

Statistical analysis

SPSS 20.0 was used to analyze the data of the observation indicators (potential risk factors) one by one. For pairwise comparisons of groups, we used the χ2 test or Fisher’s exact test for categorical variables and Student’s t test for quantitative variables. Multivariable logistic regression was conducted to determine the independent risk factors. P < 0.05 was considered statistically significant.

RESULTS

Seventy older patients with CBDS underwent LCBDE. There were 58 patients without bile leakage and 12 with bile leakage. There were 15 patients (21.4%) with diabetes mellitus, 42 (60%) with hypertension, 22 (31.4%) with pulmonary disease, 12 (17.4%) with heart disease, and 12 with cerebrovascular disease. There were no significant differences in demographic data or clinical characteristics between the two groups (Table 1). Univariate analysis was performed on the observed indicators. Positive culture of bile bacteria was identified to be a risk factor for bile leakage after LCBDE in older patients with CBDS (P < 0.05) (Table 2). This study had one limitation: Because of its retrospective nature, missing data were an inherent problem (missing data are marked with 1) (Table 2). Because they were missing at random, and the number of missing data points was small, we used the multiple imputation method to fill in the missing data, so the results are still considered reliable[19].

Table 1 Demographic data and clinical characteristics of older patients with common bile duct stones.
Characteristic
Non-bile leakage
Bile leakage
P value
Sex
Male2651.000
Female327-
Age (years), mean ± SD77.10 ± 5.48379.09 ± 6.7880.278
Diabetes mellitus
Yes1050.136
No487-
Hypertension
Yes3390.400
No253-
Pulmonary disease
Yes1660.128
No426-
Heart disease
Yes930.709
No499-
Cerebrovascular disease
Yes930.709
No499-
ASA score
II4490.433
III132-
IV11-
Table 2 Analysis of factors related to bile leakage after laparoscopic common bile duct exploration.
Characteristic
Non-bile leakage
Bile leakage
P value
Sex
Male2651.000
Female327-
Age (years), mean ± SD77.10 ± 5.48379.09 ± 6.7880.278
Viral hepatitis B
Yes211.000
No5611-
Diabetes mellitus
Yes1050.136
No487-
Hypertension
Yes3390.400
No253-
White blood cell count
< 10 × 109/L51120.343
≥ 10 × 109/L70-
Percentage of neutrophils
< 70%3271.000
≥ 70%265-
Hemoglobin
< 120 g/L3190.292
≥ 120 g/L273-
Total bilirubin
< 34.2 μmol/L4160.165
≥ 34.2 μmol/L176-
Direct bilirubin
< 17.1 μmol/L3960.256
≥ 17.1 μmol/L196-
Indirect bilirubin
< 17.1 μmol/L4391.000
≥ 17.1 μmol/L153-
Alanine transaminase
< 80 U/L2980.462
≥ 80 U/L294-
Aspartate aminotransferase
< 70 U/L3981.000
≥ 70 U/L194-
Alkaline phosphatase
< 100 U/L1221.000
≥ 100 U/L4610-
γ-glutamyl transpeptidase
< 45 U/L520.751
≥ 45 U/L5310-
Total bile acid
< 13 μmol/L3860.311
≥ 13 μmol/L206-
Total cholesterol1
< 5.7 mmol/L49120.341
≥ 5.7 mmol/L90-
High-density lipoprotein cholesterol1
< 1.55 mmol/L45110.476
≥ 1.55 mmol/L131-
Low-density lipoprotein cholesterol1
< 3.36 mmol/L46110.552
≥ 3.36 mmol/L121-
Amylase
< 133 U/L50101.000
≥ 133 U/L82-
Total protein
< 65 g/L3690.603
≥ 65 g/L223-
Albumin
< 35 g/L2860.913
≥ 35 g/L306-
Associated cholecystectomy
Yes57121.000
No10-
Stone position
Upper1140.473
Lower ends478-
Number of stones
≤ 12340.933
> 1358-
Stone size
< 10 mm1550.452
≥ 10 mm437-
Diameter of CBDSs
< 10 mm620.898
≥ 10 mm5210-
Operation mode
PDC3240.345
T-tube drainage217-
PDC + ENBD51-
Abdominal surgery history
Yes1440.764
No448-
Periampullary diverticula
Yes420.593
No5410-
Postoperative fasting time
≤ 1 day3390.400
> 1 day253-
Bacterial culture of bile1
Negative261< 0.05
Positive3211-

We subdivided the results into bile bacteria in patients without bile leakage and bile bacteria in patients with bile leakage (Table 3). The distribution of bile bacteria in patients with bile leakage was different from that in patients without. To compare the effects of different species of bile bacteria on risk factors for bile leakage after LCBDE in older patients with CBDS, we conducted further analysis. Univariate analysis showed that Enterococcus faecalis (E. faecalis) and Pseudomonas aeruginosa (P. aeruginosa) were associated with an increased risk of postoperative bile leakage (P < 0.05). Multivariate analysis showed that E. faecalis was an independent risk factor for postoperative bile leakage in older patients with CBDS (P < 0.05) (Table 4). According to the results of the drug sensitivity analysis, the bacteria were divided into susceptible, intermediate, and resistant groups. The results showed that E. faecalis was fully susceptible to ampicillin, penicillin, vancomycin, linezolid, and furantoin (Figure 1).

Figure 1
Figure 1 Drug sensitivity analysis of Enterococcus faecalis.
Table 3 Distribution of bile bacteria after laparoscopic common bile duct exploration in older patients with common bile duct stones.
Bile bacteria
Non-bile leakage
Bile leakage
Enterococcus faecalis34
Escherichia coli51
Enterococcus faecium41
Klebsiella pneumoniae22
Enterococcus gallinarum31
Enterobacter cloacae21
Pseudomonas aeruginosa02
Aeromonas caviae01
Staphylococcus aureus10
Staphylococcus hemolyticus10
Actinomyces israeli10
Enterococcus hirae01
Morganella morganii10
Klebsiella oxytoca10
Polymicrobial53
Table 4 Effect of different bile culture bacterial types on bile leakage in older patients with common bile duct stones after laparoscopic common bile duct exploration.
Bacteria
Non-bile leakage
Bile leakage
P value
Logistic regression analysis (P value, OR, 95%CI)
Enterococcus faecalis
Yes34< 0.05< 0.05, 7.857, 1.321-46.438
No537--
Escherichia coli
Yes511.000-
No4310--
Enterococcus faecium
Yes411.000-
No4410--
Klebsiella pneumoniae
Yes220.316-
No469--
Enterococcus gallinarum
Yes311.000-
No4510--
Pseudomonas aeruginosa1
Yes02< 0.05NA, NA, NA
No489--
Aeromonas caviae
Yes010.186-
No4810--
Monomicrobia4180.356-
Polymicrobial53--
DISCUSSION

According to Goldman’s index of cardiac risk, it was often believed that patients over the age of 70 years had a higher risk of surgery. However, with the development of medical technology, LCBDE is currently considered a safe and effective treatment for older patients with CBDSs[20,21]. Bile leakage is a serious complication after LCBDE, and the probability of occurrence is 3.8%-15.3%[22-24]. Some studies have shown that the mortality rate of postoperative bile leakage can be as high as 10%[25,26], especially in older patients, as the immune system and resistance of elderly patients are weaker, and they often have comorbid heart disease, cerebrovascular disease, pulmonary disease, diabetes mellitus, and other related diseases. When bile leakage occurs in elderly patients with CBDS after surgery, the risk of death will be increased[13-16]. Although most cases of bile leakage can be improved after conservative treatment or ERCP stent drainage, it costs patients much time and money and causes pain. In terms of the long-term prognosis, bile leakage can lead to an increase in the probability of malignant tumors of the bile duct[27]. Therefore, it is important to reduce the occurrence of bile leakage as much as possible.

At present, there are few studies on the risk factors for bile leakage after LCBDE for older patients with CBDSs, so there is currently no effective clinical guidance available. The results of this study show that positive culture of bile bacteria was a risk factor for bile leakage after LCBDE in older patients with CBDSs. It has been found that positive cultures of bile bacteria can lead to an increased risk of postoperative wound infection, and bacterial cultures taken from the infectious site were similar to the bile flora of the patients[28]. Although there has been no study on the mechanism of bacterial infection and bile leakage, according to studies on bacterial infection and colorectal anastomotic leakage, after bacterial colonization around the anastomosis site, E. faecalis and P. aeruginosa can release collagenase[29-32]; however, collagen plays an important role in the healing of the anastomosis. Therefore, we speculate that this may be because bile-containing bacteria flow out of the bile duct after incision of the duct, causing bacterial colonization around the incision site. By releasing collagenase, the bacteria affect the healing of the bile duct incision, eventually leading to bile leakage.

It is generally considered that bile is sterile, and a positive bile culture often indicates acute or chronic cholangitis[33]. It is a common cause of abdominal infection and life-threatening conditions, and mortality rates can be as high as 9%-12% in older patients[34]. In this study, a total of 14 species of bacteria were found in bile culture, but no fungal infections were found. Among 14 species of bacteria identified, Gram-negative bacteria accounted for 47.4%, and Gram-positive bacteria accounted for 52.6%. The top five bile bacteria were E. faecalis (7 strains, 18.9%), Escherichia coli (6 strains, 16.2%), Enterococcus faecium (5 strains, 13.5%), Klebsiella pneumoniae (4 strains, 10.8%), and Enterococcus gallinarum (4 strains, 10.8%), which is similar to other studies[28,35,36]. We found that E. faecalis was an independent risk factor for bile leakage after LCBDE in older patients with CBDSs. Although our univariate analysis showed that P. aeruginosa was also a risk factor for bile leakage after LCBDE in older patients with CBDSs, because the number was small, multivariate analysis could not be performed, which was a limitation of this study.

We conducted antibiotic sensitivity analysis on E. faecalis and found that it was 100% susceptible to penicillin, ampicillin, linezolid, vancomycin, and furantoin, and > 85% susceptible to ciprofloxacin, levofloxacin, gentamicin, and streptomycin. This is similar to other studies[37-39]. Although there are many studies on bile microorganisms and drug sensitivity analysis, because of the worldwide increase in multidrug-resistant bacteria, the choice of antibiotic treatment options remains a challenge for clinicians. Antibiotic selection and timely use are important for improving the prognosis of patients[40]. Studies have found that inadequate initial antimicrobial therapy is associated with increased 30-day mortality in patients with bacterial cholangitis[41-43]. The results of bacterial susceptibility analysis of bile culture in this center were obtained on days 3-4 after surgery. However, some of the 12 patients developed bile leakage within 3 days after surgery; therefore, the correct empiric antibiotic regimen before and after surgery is important. Some studies have found that E. faecalis is associated with the occurrence of postoperative complications of biliary tract diseases[28,44], and Nitzan et al[36] found that deaths in patients with acute cholangitis may be related to the empiric regimen not covering Enterococcus and Candida species. Therefore, we suggest coverage with antibiotics to which E. faecalis is sensitive in the empiric regimen.

CONCLUSION

We found that E. faecalis-associated biliary tract infection is an independent risk factor for bile leakage after LCBDE in older patients with CBDSs. E. faecalis was 100% susceptible to penicillin, ampicillin, linezolid, vancomycin, and furantoin, and > 85% susceptible to ciprofloxacin, levofloxacin, gentamicin, and streptomycin. Therefore, for patients with cholangitis, we suggest coverage with antibiotics to which E. faecalis is sensitive in the empiric regimen, to reduce the incidence of postoperative bile leakage in older patients with CBDSs.

Footnotes

Provenance and peer review: Unsolicited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Gastroenterology and hepatology

Country of origin: China

Peer-review report’s classification

Scientific Quality: Grade A, Grade C, Grade D

Novelty: Grade B, Grade B, Grade C

Creativity or Innovation: Grade B, Grade B, Grade C

Scientific Significance: Grade A, Grade B, Grade B

P-Reviewer: Cheng X; Itoh K S-Editor: Bai Y L-Editor: Wang TQ P-Editor: Xu ZH

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